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Friday, February 17, 2006

Blind Watchmaker or Swiss Designer? (Part I)

Another topic I've been working on is robustness, one of the abstract nouns du jour. Robustness is defined as resistance to some kind of perturbation, such as mutation, heat-shock, or a poison. This is an old idea in biology: it is closely related, for example, to CH Waddington's "canalization", and to Claude Bernard's "homeostasis". It also has obvious parallels in other fields, such as the concept of "stability" in community ecology and "control theory" in engineering.

What fascinates biologists is that organisms appear to be riddled with robustness to all sorts of perturbations. This seems to be true at all levels of biological organization, from the genetic code to metabolic pathways, from RNA and protein structure to genetic regulatory networks. This robustness has important evolutionary consequences because it affects the expression of phenotypic variation within populations, the fuel for natural selection. (For a detailed survey of these topics I'd recommend a book I'm reading at the moment: "Robustness and Evolvability in Living Systems" by Andreas Wagner. Some chapters are previewed in his recent papers. Or you can listen to this talk.)

To make some of these issues clearer I'll discuss a concrete example reported in a paper by Wagner ("Circuit topology and the evolution of robustness in two-gene circadian oscillators". PNAS 102: 11775–11780, 2005). One class of biological systems that has been shown to be highly robust are the genetic oscillators underlying circadian rhythms (i.e., endogenous activity cycles with a period of approximately 24h) in a variety of organisms, including cyanobacteria, fungi, insects and mammals. Although some of these clocks may have evolved independently, they tend to share some basic characteristics according to Wagner:

"First, the principal clock mechanism is simple. It minimally involves one gene that is expressed to produce a mRNA and a protein product that may undergo further modification and exerts direct or indirect negative feedback on the expression of its own gene. Examples include the frequency (frq) gene in the fungus Neurospora crassa, the timeless (tim) gene in the fruit fly Drosophila melanogaster, and the kaiC gene in the cyanobacterium Synechococcus spp. This simple mechanism will generate sustained oscillations in protein concentrations only if the negative feedback is slow. That is, there must be a delay between the time at which the gene product's concentration rises because of its expression and the time at which the gene product represses its own expression. [...] The second common feature of many circadian oscillators is that they consist of not one but two or more oscillating gene products whose regulation is linked. This holds in organisms as different as the fungus Neurospora, the fruit fly Drosophila, and mammals."

More interestingly, like Swiss watches, they show remarkable accuracy and precision under a range of conditions. In his paper, Wagner asks:

"[W]hether interlocked circadian oscillators may be an accident of life's history (there are infinitely many ways to obtain limit cycle oscillations in regulatory systems), or whether such interlocking may exist because it provides especially robust oscillations."

There is, of course, another, if less scientific, alternative that Wagner forgot to mention: that an intelligent designer decided to make circadian clocks that way. Maybe the designer was even Swiss! William Paley seems to have been thinking about this problem two centuries ago:

"But suppose I had found a watch upon the ground, and it should be inquired how the watch happened to be in that place. [...] When we come to inspect the watch, we perceive [...] that its several parts are framed and put together for a purpose [...]; that, if the different parts had been differently shaped from what they are, of a different size from what they are, or placed after any other manner, or in any other order, than that in which they are placed, either no motion at all would have been carried on in the machine, or none which would have answered the use that is now served by it. [...] This mechanism being observed [...], the inference, we think, is inevitable, that the watch must have had a maker: that there must have existed, at some time, and at some place or other, an artificer or artificers who formed it for the purpose which we find it actually to answer; who comprehended its construction, and designed its use."